Regional Specialisation of T Cell Subsets and Apoptosis in the Human Gut Mucosa: Differences Between Ileum and Colon in Healthy Intestine and Inflammatory Bowel Diseases

Background and Aims: There is very limited information regarding region-specific immunological response in human intestine. We aimed to determine differences in immune compartmentalisation between ileum and colon in healthy and inflamed mucosa. Methods: T cell profile and its apoptosis were measured by flow cytometry, Th1, Th17, Treg [CD4+CD25+FOXP3+], double positive [DP, CD3+CD4+CD8+] and double negative T cells [DN, CD3+CD4-CD8-], immunohistochemistry \[FOXP3, caspase-3], and real-time polymerase chain reaction [PCR\] \[IFN-γ, IL-17-A, and FOXP3\] on biopsies from different regions of healthy intestine and of intestine in inflammatory bowel diseases. Results: Healthy colon showed higher percentages of Treg, Th17, and DN, and lower numbers of DP T cells compared with ileum [ p < 0.05]. Some but not all region-specific differences were lost in inflammatory conditions. Disease-specific patterns were found: a Th1/Th17 pattern and a Th17 pattern in Crohn’s disease and ulcerative colitis respectively, whereas a reduction in Th1/Th17 was found in microscopic colitis. In colonic Crohn’s disease and microscopic colitis, DN T cells had a pattern inverse to that of Th1/Th17 (increase in microscopic colitis [ p < 0.05] and decrease in Crohn’s disease [ p < 0.005]). Higher levels of lymphocyte apoptosis were found in healthy colon compared with the ileal counterparts [ p = 0.001]. All forms of colonic inflammation presented a dramatic decrease in apoptosis compared with healthy colon. By contrast ileal Crohn’s disease showed higher levels of cleaved-Caspase+ CD3+ cells. Conclusions: Immunological differences exist in healthy gastrointestinal tract. Inflammatory processes overwhelm some location-specific differences, whereas others are maintained. Care has to be taken when analysing immune response in intestinal inflammation, as location-specific differences may be relevant.